Analytical challenges in chemical-enzymatic drug targeting

The development of new methods of chemical enzymatic drug targeting (chemical delivery systems and soft drugs) relies on specific and sensitive analytical techniques. High-performance liquid chromatography has been a powerful technique that can separate complex mixtures of chemical species involved in the enzymatic and/or chemical transformation in vivo and in vitro to produce the targeted drug. The successful chemical separation requires specificity of interaction of the chromatographic column and the solute to resolve compounds with characteristic (sometimes subtle) chemical differences. Differing lipophilicity and the ionic or neutral nature of the species are the primary factors to be considered during method development. Improving the specificity toward the analyte has often been necessary to provide adequate detection limits for tissue samples derived from the site of action. Chromatography lacks, however, the power of identifying unknown species. Mass spectrometry, both coupled with chromatography and as a technique providing direct specificity, may represent a viable solution. These issues, including future perspectives, are discussed in this review.